Research

Infective parasites must traverse the mosquito salivary glands to transmit malaria to humans and other animals. The Andrew Lab is leveraging its findings on the molecules required to form and maintain the Drosophila salivary gland to develop strategies to block malaria transmission. Shown is an optical section through the distal lateral lobe of a female adult salivary gland stained with DAPI (blue, nuclei), alpha-tubulin (green, cytosol) and wheat-germ agglutinin (red; chitin/O-GlcNAcylated proteins).

To maintain homeostasis, cells need to measure the concentration of molecules such as nutrients, reactants, and products. Eukaryotic cells, whether single-cell fungi or part of a complex human organ, require environmental oxygen for essential reactions. Consequently, cells possess mechanisms to sense and adapt to changes in oxygen supply. The hypoxia-inducible factor (HIF) is a key regulator of these adaptive responses in metazoans.

Among the earliest inputs that cells experienced, mechanical stress (forces) guide and direct behavior of cells, including when they are part of tissues, organs, and organ systems. These mechanical stresses are propagated through the cell’s skin (the cell cortex), which is a composite material of membrane and cytoskeleton. Key molecular machinery senses the forces, and through mechanotransduction, the mechanical signals may be converted into biochemical signals, which guide cell behavior.

Research in the Ewald laboratory starts from a simple question: which cells in a breast tumor are the most dangerous to the patient and most responsible for metastatic disease? To answer this question, we developed novel 3D culture assays to allow real-time analysis of invasion. Briefly, we use enzymatic digestion to isolate thousands of “tumor organoids” from each primary tumor. Each organoid is composed of 200-500 epithelial cancer cells and reflects the cellular heterogeneity of the primary tumor.

Biological oscillations are universally found in nature and are critical at many levels of cellular organization. In the model organism we study, the social amoeba Dictyostelium discoideum, starvation-triggered cell-cell aggregation and developmental morphogenesis are orchestrated by periodic extracellular cAMP waves, which provide both gradients for chemotactic migration and signals for development. Repeated occupancy of the G protein–coupled cAMP receptors promotes optimal developmental gene expression, whereas continuous stimulation suppresses the program.